This Phase I project is to evaluate a series of novel drug combinations to prevent and treat wound infections. Wounds have certain characteristics that promote the development of infections: the presence of devitalized tissue, foreign bodies, clots, fluid collections, and contamination of wounds with bacteria from the casualty's skin, the environment and the hospital. Medical reports from the military actions in Iraq and Afghanistan confirmed the emergence of multi-drug resistant bacteria (MDR) such as Acinetobacter baumannii, Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus, and multi-drug resistant Pseudomonas aeruginosa. Infections caused by these multi-drug resistant organisms appear to result in significant morbidity and mortality. Bacteria within biofilms are inherently insensitive to antiseptics, microbicides, and host immune system. To complicate the problem further, the MDR bacteria can form biofilm at the wound sites or implant surfaces, causing infections that are insensitive to host immune system and antibiotic therapies. An effective antimicrobial strategy to prevent and treat biofilm is desperately needed in both military and civilian care. In this project, we propose a series of novel drug combinations as antibiofilm formulations. Efficacy of the antibiofilm formulations will be assessed in a wound dressing model using nanofibrillar chitosan meshes as a topical delivery carrier. The proposed technology combines characteristics including nanofibrillar barrier, hemostatic activity, antibiofilm efficacy, and controlled release strategy. PUBLIC HEALTH RELEVANCE: It was estimated that nosocomial infections affect about 2.0 M people in the U.S. each year and costs more than $11.0 B to the healthcare providers. Wound care and indwelling catheters, the two most commonly associated areas of infection, experienced a surge of antimicrobial devices in the 1990s. By 2007, the US wound care market has grown to an estimated $10 B. This growth has driven efforts to reduce infection that resulted in the development of antimicrobial dressings.